Karel T. Koch

A systematic review and meta-analysis of intra-aortic balloon pump therapy in ST-elevation myocardial infarction : should we change the guidelines?

Aims Intra-aortic balloon counterpulsation (IABP) in ST-segment elevation myocardial infarction (STEMI) with cardiogenic shock is strongly recommended (class IB) in the current guidelines. We performed meta-analyses to evaluate the evidence for IABP in STEMI with and without cardiogenic shock. Methods and results Medical literature databases were scrutinized to identify randomized trials comparing IABP with no IABP in STEMI. In absence of randomized trials, cohort studies of IABP in STEMI with cardiogenic shock were identified. Two separate meta-analyses were performed respectively. The first meta-analysis included seven randomized trials (n = 1009) of STEMI. IABP showed neither a 30-day survival benefit nor improved left ventricular ejection fraction, while being associated with significantly higher stroke and bleeding rates. The second meta-analysis included nine cohorts of STEMI patients with cardiogenic shock (n = 10529). In patients treated with thrombolysis, IABP was associated with an 18% [95% confidence interval (CI), 16-20%; P < 0.0001] decrease in 30 day mortality, albeit with significantly higher revascularization rates compared to patients without support. Contrariwise, in patients treated with primary percutaneous coronary intervention, IABP was associated with a 6% (95% CI, 3-10%; P < 0.0008) increase in 30 day mortality. Conclusion The pooled randomized data do not support IABP in patients with high-risk STEMI. The meta-analysis of cohort studies in the setting of STEMI complicated by cardiogenic shock supported IABP therapy adjunctive to thrombolysis. In contrast, the observational data did not support IABP therapy adjunctive to primary PCI. All available observational data concerning IABP therapy in the setting of cardiogenic shock is importantly hampered by bias and confounding. There is insufficient evidence endorsing the current guideline recommendation for the use of IABP therapy in the setting of STEMI complicated by cardiogenic shock. Our meta-analyses challenge the current guideline recommendations.

Familial Sudden Death Is an Important Risk Factor for Primary Ventricular Fibrillation A Case-Control Study in Acute Myocardial Infarction Patients

Background— Primary ventricular fibrillation (VF) accounts for the majority of deaths during the acute phase of myocardial infarction. Identification of patients at risk for primary VF remains very poor. Methods and Results— We performed a case-control study in patients with a first ST-elevation myocardial infarction (STEMI) to identify independent risk factors for primary VF. A total of 330 primary VF survivors (cases) and 372 controls were included; patients with earlier infarcts or signs of structural heart disease were excluded. Baseline characteristics, including age, gender, drug use, and ECG parameters registered well before the index infarction, as well as medical history, were not different. Infarct size and location, culprit coronary artery, and presence of multivessel disease were similar between groups. Analysis of ECGs performed at hospital admission for the index STEMI revealed that cumulative ST deviation was significantly higher among cases (OR per 10-mm ST deviation 1.59, 95% CI 1.25 to 2.02). Analysis of medical histories among parents and siblings showed that the prevalence of cardiovascular disease was similar between cases and controls (73.1% and 73.0%, respectively); however, familial sudden death occurred significantly more frequently among cases than controls (43.1% and 25.1%, respectively; OR 2.72, 95% CI 1.84 to 4.03). Conclusions— In a population of STEMI patients, the risk of primary VF is determined by cumulative ST deviation and family history of sudden death.

Plaque Instability Frequently Occurs Days or Weeks Before Occlusive Coronary Thrombosis A Pathological Thrombectomy Study in Primary Percutaneous Coronary Intervention

Background—Acute ST-elevation myocardial infarction (STEMI) is caused by sudden occlusive coronary thrombosis, after plaque disruption; however, a considerable time interval between plaque disturbance and the onset of symptoms has been suggested. We therefore studied the age of intracoronary thrombi, aspirated during angioplasty in patients with acute STEMI. Methods and Results—Percutaneous intracoronary thrombectomy during angioplasty was performed in 211 consecutive STEMI patients within 6 hours after onset of anginal symptoms. The aspirated material was histologically screened on thrombus and plaque components, and thrombus age was classified as fresh (<1 day), lytic thrombus (1 to 5 days), and organized thrombus (>5 days). In all patients, intracoronary-derived material was retrieved in the filter of the collection bottle. Thrombus was identified in 199 (95%) of 211 patients. In 12 patients (5%), only plaque components were identified, and in 85 patients (41%), both thrombus and plaque material were aspirated. In 18 (9%) of 199 patients, the thrombus was organized, and in 70 patients (35%), the thrombus showed lytic changes, whereas in 98 (49%), a completely fresh thrombus was found. In 14 (7%) of 199 patients, the thrombus showed combined features of both fresh thrombus and organized thrombus. Conclusions—In at least 50% of patients with acute STEMI, coronary thrombi were days or weeks old. This indicates that sudden coronary occlusion is often preceded by a variable period of plaque instability and thrombus formation, initiated days or weeks before onset of symptoms.

Physiological Basis and Long-Term Clinical Outcome of Discordance Between Fractional Flow Reserve and Coronary Flow Velocity Reserve in Coronary Stenoses of Intermediate Severity

Background—Discordance between fractional flow reserve (FFR) and coronary flow velocity reserve (CFVR) may reflect important coronary pathophysiology but usually remains unnoticed in clinical practice. We evaluated the physiological basis and clinical outcome associated with FFR/CFVR discordance. Methods and Results—We studied 157 intermediate coronary stenoses in 157 patients, evaluated by FFR and CFVR between April 1997 and September 2006 in which revascularization was deferred. Long-term follow-up was performed to document the occurrence of major adverse cardiac events: cardiac death, myocardial infarction, or target vessel revascularization. Discordance between FFR and CFVR occurred in 31% and 37% of stenoses at the 0.75, and 0.80 FFR cut-off value, respectively, and was characterized by microvascular resistances during basal and hyperemic conditions. Follow-up duration amounted to 11.7 years (Q1–Q3, 9.9–13.3 years). Compared with concordant normal results of FFR and CFVR, a normal FFR with an abnormal CFVR was associated with significantly increased major adverse cardiac events rate throughout 10 years of follow-up, regardless of the FFR cut-off applied. In contrast, an abnormal FFR with a normal CFVR was associated with equivalent clinical outcome compared with concordant normal results: ⩽3 years when FFR <0.75 was depicted abnormal and throughout 10 years of follow-up when FFR ⩽0.80 was depicted abnormal. Conclusions—Discordance of CFVR with FFR originates from the involvement of the coronary microvasculature. Importantly, the risk for major adverse cardiac events associated with FFR/CFVR discordance is mainly attributable to stenoses where CFVR is abnormal. This emphasizes the requirement of intracoronary flow assessment in addition to coronary pressure for optimal risk stratification in stable coronary artery disease.

Hyperemic Stenosis Resistance Index for Evaluation of Functional Coronary Lesion Severity

Background—Both coronary blood flow velocity reserve (CFVR) and myocardial fractional flow reserve (FFR) are used to evaluate the hemodynamic severity of coronary lesions. However, discordant results between CFVR and FFR have been observed in 25% to 30% of intermediate coronary lesions. An index of stenosis resistance based on a combination of intracoronary pressure and flow velocity may improve the assessment of functional coronary lesion severity. Methods and Results—Single photon emission computed tomography (SPECT) was performed in 151 patients with angina to determine reversible perfusion defects within one-week before cardiac catheterization. Coronary pressure and flow velocity was measured distal to 181 single coronary lesions with a mean diameter stenosis of 56% (range: 32% to 85%). Maximum hyperemia was induced by 15 to 20 &mgr;g IC adenosine to determine CFVR, FFR, and the hyperemic stenosis resistance index (h-SRv), defined as the ratio of hyperemic stenosis pressure gradient (mean aorta pressure-mean distal pressure) and hyperemic average peak-flow velocity. Receiver-operating-characteristic curves of CFVR, FFR, and h-SRv were calculated to evaluate the predictive value for presence of reversible perfusion defects on SPECT with the use of the area under curve (AUC). The AUC was significantly higher for h-SRv (0.90±0.03) compared with those for CFVR (0.80±0.04;P =0.024) and FFR (0.82±0.03;P =0.018), respectively. Agreement with SPECT was particularly higher (73%) than for CFVR (49%, P =0.022) or FFR (51%, P =0.037) in the group of lesions showing discordant results between CFVR and FFR Conclusion—These results indicate that hyperemic stenosis resistance index is a more powerful predictor of reversible perfusion defects than CFVR or FFR.

Factors associated with cardiac conduction disorders and permanent pacemaker implantation after percutaneous aortic valve implantation with the CoreValve prosthesis

BACKGROUND Cardiac conduction disorders and requirement for permanent pacemaker implantation (PPI) are not uncommon after surgical aortic valve replacement and have important clinical implications. We aimed to investigate the incidence of cardiac conduction disorders after percutaneous aortic valve implantation (PAVI) and to identify possible clinical factors associated with their development. METHODS We studied 34 patients (mean age 80 +/- 8 years, 18 male) who underwent PAVI with the CoreValve bioprosthesis (Corevalve Inc, Irvine, CA). Electrocardiographic evaluation was performed pre- and postprocedurally, and at 1-week and 1-month follow-up. Other clinical variables were obtained from the medical history, echocardiography, and angiography. RESULTS After PAVI, 7 patients required PPI, all of whom developed total atrioventricular block within 3 days postprocedurally. A smaller left ventricular outflow tract diameter (20.3 +/- 0.5 vs 21.6 +/- 1.8 cm, P = .01), more left-sided heart axis (-20 degrees +/- 29 degrees vs 19 degrees +/- 36 degrees , P = .02), more mitral annular calcification (10 +/- 1 vs 5 +/- 4 mm, P = .008), and a smaller postimplantation indexed effective orifice area (0.86 +/- 0.20 vs 1.10 +/- 0.26 cm(2)/m(2), P = .04) were associated with PPI. The incidence of new left bundle-branch block (LBBB) was 65% and was associated with a deeper implantation of the prosthesis: 10.2 +/- 2.3 mm in the new-LBBB group versus 7.7 +/- 3.1 mm in the non-LBBB group (P = .02). CONCLUSIONS Percutaneous aortic valve implantation with the CoreValve prosthesis results in a high incidence of total atrioventricular block requiring PPI and new-onset LBBB. Preexisting disturbance of cardiac conduction, a narrow left ventricular outflow tract, and the severity of mitral annular calcification predict the need for permanent pacing, whereas the only factor shown to be predictive for new-onset LBBB is the depth of prosthesis implantation.

Bioresorbable Scaffolds versus Metallic Stents in Routine PCI

BACKGROUND Bioresorbable vascular scaffolds were developed to overcome the shortcomings of drug‐eluting stents in percutaneous coronary intervention (PCI). We performed an investigator‐initiated, randomized trial to compare an everolimus‐eluting bioresorbable scaffold with an everolimus‐eluting metallic stent in the context of routine clinical practice. METHODS We randomly assigned 1845 patients undergoing PCI to receive either a bioresorbable vascular scaffold (924 patients) or a metallic stent (921 patients). The primary end point was target‐vessel failure (a composite of cardiac death, target‐vessel myocardial infarction, or target‐vessel revascularization). The data and safety monitoring board recommended early reporting of the study results because of safety concerns. This report provides descriptive information on end‐point events. RESULTS The median follow‐up was 707 days. Target‐vessel failure occurred in 105 patients in the scaffold group and in 94 patients in the stent group (2‐year cumulative event rates, 11.7% and 10.7%, respectively; hazard ratio, 1.12; 95% confidence interval [CI], 0.85 to 1.48; P=0.43); event rates were based on Kaplan–Meier estimates in time‐to‐event analyses. Cardiac death occurred in 18 patients in the scaffold group and in 23 patients in the stent group (2‐year cumulative event rates, 2.0% and 2.7%, respectively), target‐vessel myocardial infarction occurred in 48 patients in the scaffold group and in 30 patients in the stent group (2‐year cumulative event rates, 5.5% and 3.2%), and target‐vessel revascularization occurred in 76 patients in the scaffold group and in 65 patients in the stent group (2‐year cumulative event rates, 8.7% and 7.5%). Definite or probable device thrombosis occurred in 31 patients in the scaffold group as compared with 8 patients in the stent group (2‐year cumulative event rates, 3.5% vs. 0.9%; hazard ratio, 3.87; 95% CI, 1.78 to 8.42; P<0.001). CONCLUSIONS In this preliminary report of a trial involving patients undergoing PCI, there was no significant difference in the rate of target‐vessel failure between the patients who received a bioresorbable scaffold and the patients who received a metallic stent. The bioresorbable scaffold was associated with a higher incidence of device thrombosis than the metallic stent through 2 years of follow‐up. (Funded by Abbott Vascular; AIDA ClinicalTrials.gov number, NCT01858077.)

Haplotype-Sharing Analysis Implicates Chromosome 7q36 Harboring DPP6 in Familial Idiopathic Ventricular Fibrillation

Idiopathic Ventricular Fibrillation (IVF) is defined as spontaneous VF without any known structural or electrical heart disease. A family history is present in up to 20% of probands with the disorder, suggesting that at least a subset of IVF is hereditary. A genome-wide haplotype-sharing analysis was performed for identification of the responsible gene in three distantly related families in which multiple individuals died suddenly or were successfully resuscitated at young age. We identified a haplotype, on chromosome 7q36, that was conserved in these three families and was also shared by 7 of 42 independent IVF patients. The shared chromosomal segment harbors part of the DPP6 gene, which encodes a putative component of the transient outward current in the heart. We demonstrated a 20-fold increase in DPP6 mRNA levels in the myocardium of carriers as compared to controls. Clinical evaluation of 84 risk-haplotype carriers and 71 noncarriers revealed no ECG or structural parameters indicative of cardiac disease. Penetrance of IVF was high; 50% of risk-haplotype carriers experienced (aborted) sudden cardiac death before the age of 58 years. We propose DPP6 as a gene for IVF and increased DPP6 expression as the likely pathogenetic mechanism.

Fractional flow reserve, absolute and relative coronary blood flow velocity reserve in relation to the results of technetium-99m sestamibi single-photon emission computed tomography in patients with two-vessel coronary artery disease.

OBJECTIVES We sought to perform a direct comparison between perfusion scintigraphic results and intracoronary-derived hemodynamic variables (fractional flow reserve [FFR]; absolute and relative coronary flow velocity reserve [CFVR and rCFVR, respectively]) in patients with two-vessel disease. BACKGROUND There is limited information on the diagnostic accuracy of intracoronary-derived variables (CFVR, FFR and rCFVR) in patients with multivessel disease. METHODS Dipyridamole technetium-99m sestamibi (MIBI) single-photon emission computed tomography (SPECT) was performed in 127 patients. The presence of reversible perfusion defects in the region of interest was determined. Within one week, angiography was performed; CFVR, rCFVR and FFR were determined in 161 coronary lesions after intracoronary administration of adenosine. The predictive value for the presence of reversible perfusion defects on MIBI SPECT of CFVR, rCFVR and FFR was evaluated by the area under the curve (AUC) of the receiver operating characteristics curves. RESULTS The mean percentage diameter stenosis was 57% (range 35% to 85%), as measured by quantitative coronary angiography. Using per-patient analysis, the AUCs for CFVR (0.70 +/- 0.052), rCFVR (0.72 +/- 0.051) and FFR (0.76 +/- 0.050) were not significantly different (p = NS). The percentages of agreement with the results of MIBI SPECT were 76%, 78% and 77% for CFVR, rCFVR and FFR, respectively. Per-lesion analysis, using all 161 measured lesions, yielded similar results. CONCLUSIONS The diagnostic accuracy of three intracoronary-derived hemodynamic variables, as compared with the results of perfusion scintigraphy, is similar in patients with two-vessel coronary artery disease. Cut-offvalues of 2.0 for CFVR, 0.65 for rCFVR and 0.75 for FFR can be used for clinical decision-making in this patient cohort. Discordant results were obtained in 23% of the cases that require prospective evaluation for appropriate patient management.

Usefulness of fractional flow reserve for risk stratification of patients with multivessel coronary artery disease and an intermediate stenosis

Intracoronary-derived, pressure-based fractional flow reserve (FFR) is important for clinical decision-making in patients with 1-vessel coronary artery disease (CAD). In the present study, we investigated the prognostic value of FFR in patients with intermediate stenoses and multivessel CAD. Therefore, we analyzed 107 patients with stable angina pectoris who underwent myocardial perfusion scintigraphy and showed no perfusion defects in the region of the intermediate lesion. At angiography, FFR was determined distal to the intermediate lesion. FFR was abnormal (i.e., <0.75) in 15 of 107 stenoses (14%). Angioplasty of the intermediate stenosis was deferred based on the absence of a perfusion defect. Patients were followed for 1 year to document major cardiac events related to the intermediate lesion. At 1-year follow-up, a total of 12 (11%: no deaths, 3 myocardial infarctions, 2 coronary bypass operations, 7 coronary angioplasties) events occurred in the entire group that were related to the intermediate lesion. The event rate was significantly higher when angioplasty was deferred despite FFR <0.75 compared with the group with FFR > or = 0.75 (4 of 15 [27%] vs 8 of 92 [9%]; p <0.041). The relative risk of FFR for predicting cardiac events (mainly revascularization procedures) was 3.1 (95% confidence interval 1.1 to 8.9; p <0.05). In conclusion, deferral of angioplasty of intermediate coronary narrowings is safe based on FFR > or = 0.75 in this patient cohort; this coincides with previous reports in patients with 1-vessel CAD. Furthermore, these results suggest that FFR is more useful than single-photon emission computed tomography for clinical decision-making and risk stratification in patients with multivessel CAD.